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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

HSPB1 influences mitochondrial respiration in ER-stressed beta cells

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Author(s):
Mule, Simon Ngao [1] ; Gomes, Vinicius De Morais [2, 1] ; Wailemann, Rosangela A. M. [2] ; Macedo-da-Silva, Janaina [1] ; Rosa-Fernandes, Livia [1] ; Larsen, Martin R. [3] ; Labriola, Leticia [2] ; Palmisano, Giuseppe [1]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, GlycoProte Lab, Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Inst Chem, Dept Biochem, Av Prof Lineu Prestes 748, BR-05508000 Sao Paulo - Brazil
[3] Univ Southern Denmark, Dept Biochem & Mol Biol, Odense - Denmark
Total Affiliations: 3
Document type: Journal article
Source: BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS; v. 1869, n. 9 SEP 2021.
Web of Science Citations: 0
Abstract

Beta-cell death and dysfunction are involved in the development of type 1 and 2 diabetes. ER-stress impairs betacells function resulting in pro-apoptotic stimuli that promote cell death. Hence, the identification of protective mechanisms in response to ER-stress could lead to novel therapeutic targets and insight in the pathology of these diseases. Here, we report the identification of proteins involved in dysregulated pathways upon thapsigargin treatment of MIN6 cells. Utilizing quantitative proteomics we identified upregulation of proteins involved in protein folding, unfolded protein response, redox homeostasis, proteasome processes associated with endoplasmic reticulum and downregulation of TCA cycle, cellular respiration, lipid metabolism and ribosome assembly processes associated to mitochondria and eukaryotic initiation translation factor components. Subsequently, pro-inflammatory cytokine treatment was performed to mimic pathological changes observed in beta-cells during diabetes. Cytokines induced ER stress and impaired mitochondrial function in beta-cells corroborating the results obtained with the proteomic approach. HSPB1 levels are increased by prolactin on pancreatic beta-cells and this protein is a key factor for cytoprotection although its role has not been fully elucidated. Here we show that while up-regulation of HSPB1 was able to restore the mitochondrial dysfunction induced by beta-cells' exposure to inflammatory cytokines, silencing of this chaperone abrogated the beneficial effects promoted by PRL. Taken together, our results outline the importance of HSPB1 to mitigate beta-cell dysfunction. Further studies are needed to elucidate its role in diabetes. (AU)

FAPESP's process: 17/04032-5 - Dissecting the pathogenesis of Chagas Disease by deep glycomics and glycoproteomics approaches
Grantee:Simon Ngao Mule
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 14/02745-6 - Unveiling the molecular mechanisms involved in Prolactin-induced cytoprotection in Pancreatic Beta Cells.
Grantee:Rosangela Aparecida Wailemann Mansano
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 17/03618-6 - Unveiling HSPB1's role in prolactin-induced modulation of the unfolded protein response in type 1 Diabetes models
Grantee:Leticia Labriola
Support type: Regular Research Grants
FAPESP's process: 18/18257-1 - Multi-user equipment approved in grant 14/06863-3: HPLC system configured for analysis of carbohydrates, amino acidis, peptides and glycoproteins
Grantee:Giuseppe Palmisano
Support type: Multi-user Equipment Program
FAPESP's process: 16/04676-7 - Photodynamic therapy to treat breast cancer: proof of concept pre-clinical studies
Grantee:Ancély Ferreira dos Santos
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 20/04923-0 - SARS-CoV-2 glycosylation: a blueprint structural insight for understanding COVID-19 pathogenesis
Grantee:Giuseppe Palmisano
Support type: Regular Research Grants
FAPESP's process: 16/14845-0 - Applying gamification to reduce stigma towards students with Autism Spectrum Disorder in mainstream schools
Grantee:Izadora Ribeiro Perkoski
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 18/15549-1 - Post-translational modifications in Chagas Disease biological processes and diagnostics: novel methodological approaches and biological applications
Grantee:Giuseppe Palmisano
Support type: Research Grants - Young Investigators Grants - Phase 2
FAPESP's process: 21/00507-4 - Glycosylation of SARS-CoV-2 to identify the structural characteristics of COVID-19
Grantee:Vinícius de Morais Gomes
Support type: Scholarships in Brazil - Post-Doctorate